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Expressions of matrix metalloproteinase-9 (MMP-9), dentin sialophosphoprotein (DSPP), and osteopontin (OPN) at histologically negative surgical margins may predict recurrence of oral squamous cell carcinoma

2012; Impact Journals LLC; Volume: 3; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.373

1949-2553

Kalu U.E. Ogbureke, Paul Weinberger, Stephen W. Looney, Li Li, Larry W. Fisher,

Oral and gingival health research

Kalu U.E. Ogbureke 1,2,3 , Paul M. Weinberger 2 , Stephen W. Looney 1,3 , Li Li 4 , Larry W. Fisher 4 1 College of Dental Medicine, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 2 Medical College of Georgia, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 3 College of Graduate Studies, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 4 Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Building 30, Room 228, Bethesda, MD Received: January 23, 2012; Accepted: March 2, 2012; Published: March 11, 2012; Keywords: Oral Cancer, DSPP, BSP, OPN, MMPs, Tumor-Free Margin Correspondence: Kalu U.E. Ogbureke, // // Abstract Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING family of proteins: dentin sialophophoprotein (DSPP); bone sialoprotein (BSP); and osteopontin OPN are upregulated in OSCCs. In this study, we aimed to correlate the expression of DSPP, OPN and BSP as well as three SIBLING-partners, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9), at histologically-negative margins of OSCCs with tumor recurrence. Immunohistochemical analyses of the SIBLINGs and MMP expressions at histologically-negative margins of OSCC was carried out in a retrospective study of 20 patients, and the results correlated with tumor recurrence. Each protein was dichotomized as "present" (≥10% staining) or "absent" (< 10% staining). The Sensitivity, Specificity, Positive Predictive Value(PV+) and Negative Predictive Value (PV-) for recurrence was calculated for each protein, along with their overall diagnostic accuracy, calculated as: (number of true positives + number of true negatives)/ number of patients. OSCC recurred in 9 of 20 patients (45%), a ratio not significantly different from the estimated population recurrence rate of 50% (p = 0.664). Among the SIBLINGs, DSPP and OPN showed the greatest Accuracy with DSPP being more Sensitive (89%) and OPN more Specific (64%). MMP-9 showed the greatest overall Accuracy (80%), slightly less Sensitivity (67%) and more Specificity (100%), than either DSPP or OPN. MMP-9 showed a superior positive PV than either DSPP or OPN. The negative PVs of OPN and MMP-9 were almost identical, and inferior to DSPP. We conclude that DSPP, OPN, or MMP-9 expressions at histologically-negative surgical margins predict OSCC recurrence with MMP-9 being the preferred predictor. These proteins may identify patients who could benefit from more extensive resection, or from adjunct treatments such as radiotherapy.